Curcumin Induces Pancreatic Adenocarcinoma Cell Death Via Reduction of the Inhibitors of Apoptosis

• Published in: Pancreas Vol. 45; no. 1; p. 101
• Main Authors: Díaz Osterman, Carlos J, Gonda, Amber, Stiff, TessaRae, Sigaran, Ulysses, Valenzuela, Malyn May Asuncion, Ferguson Bennit, Heather R, Moyron, Ron B, Khan, Salma, Wall, Nathan R
• Format: Journal Article
• Language: English
• Published: United States 01.01.2016
• Subjects: Antineoplastic Agents, Phytogenic - metabolism; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - pathology; Cell Line, Tumor; Cell Shape - drug effects; Cell Survival - drug effects; Curcumin - metabolism; Curcumin - pharmacology; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; Inhibitor of Apoptosis Proteins - genetics; Inhibitor of Apoptosis Proteins - metabolism; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - drug effects; Time Factors
• ISSN: 1536-4828
• DOI: 10.1097/MPA.0000000000000411

The inhibitor of apoptosis (IAP) proteins are critical modulators of chemotherapeutic resistance in various cancers. To address the alarming emergence of chemotherapeutic resistance in pancreatic cancer, we investigated the efficacy of the turmeric derivative curcumin in reducing IAP protein and mRNA expression resulting in pancreatic cancer cell death. The pancreatic adenocarcinoma cell line PANC-1 was used to assess curcumin's effects in pancreatic cancer. Curcumin uptake was measured by spectral analysis and fluorescence microscopy. AlamarBlue and Trypan blue exclusion assays were used to determine PANC-1 cell viability after curcumin treatment. Visualization of PANC-1 cell death was performed using Hoffman Modulation Contrast microscopy. Western blot, and polymerase chain reaction analyses were used to evaluate curcumin's effects on IAP protein and mRNA expression. Curcumin enters PANC-1 cells and is ubiquitously present within the cell after treatment. Furthermore, curcumin reduces cell viability and induces morphological changes characteristic of cell death. Additionally, curcumin decreases IAP protein and mRNA expression in PANC-1 cells. These data demonstrate that PANC-1 cells are sensitive to curcumin treatment. Futthermore, curcumin is a potential therapeutic tool for overcoming chemotherapeutic resistance mediated by IAPs. Together, this data supports a role for curcumin as part of the therapeutic approach for the treatment of pancreatic cancer.